Sodium pump in the cardiac cytoplasmic membrane is essential for the generation and maintenance of transmembrane electro-chemical gradients and hence for the maintenance of excitability of cardiac cells. The effects of myocardial ischemia on the functional activity of sodium pump are not well understood. Digitalis has been demonstrated to inhibit cardiac Na, K ions-ATPase and sodium pump activity and produce arrhythmias. The effects of myocardial ischemia on the cellular actions of digitalis have not been extensively studied although increased incidence of arrhythmias have been reported with he use of digitalis in ischemic myocardium. The primary objective of this proposed research is to determine the effects of mycardial ischemia on the actions of digitalis. This will be achieved by studying the effects of myocardial ischemia on sodium pump activity (estimated from the ouabain-sensitive 86Rb uptake) as well as on the molecular interaction between digitalis and sodium pump and Na ions, K ions-ATPase. Secondly, the effects of other biochemical derangements accompanied myocardial ischemia, such as cationic shifts and elevation of circulating levels of catecholamines, on the cardiac responses to digitalis will also be studied. And thirdly, the effects of the cardiac stimulant action of digitalis on the magnitude of ischemic injury following coronary artery occlusion will also be studied. It is hoped that the results obtained from the present research would provide a better understanding of the basic mechanism of altered digitalis toxicity in acute myocardial infarction and ultimately improve the therapeutic index of the use of digitalis in patients with ischemic heart diseases.